Whole pancreaticoduodenal transplantations with portal (PD) and systemic venous drainage were achieved in the streptozotocin-induced diabetic rats. Porto-peripheral gradient of insulin levels during IV-GTT was abrogated in the SD group, though it was well sustained in the PD group. The SD group revealed high ketone bodies, high LDL, and low HDL levels. As pancreas transplant with PD can normalize metabolic condition generally, the portal vein is preferable site for insulin delivery. However, PD could not resolve hyperinsulinemia completely. In the next step, we examined the effect of troglitazone (TGZ) on insulin regulation after pancreas transplantation. The rations of ΣIRI/ΣPG (plasma glucose) during IV-GTT were calculated as a parameter for insulin resistance, and the value in TGZ-treated rats (0.23【plus-minus】0.11μ U/ml : mg/dl) was lower than in TGZ-free rats (0.35【plus-minus】0.05μ U/ml : mg/dl) ; thus TGZ regulated insulin levels in peripheral blood after glucose load in rats bearing pancreas graft with SD. On quantitative analysis of insulin receptor content in the hindlimb muscle, TGZ activated tyrosine-phosphorylation depending on the number of insulin receptor. This fact indicated that TGZ enhanced cellular response to insulin and reduce hyperinsulinemia after pancreas transplantation.